Abstracts from ESID
THE HEALTH OF CARRIERS OF X-LINKED CHRONIC GRANULOMATOUS DISEASE IN THE
UNITED KINGDOM
Battersby AC, Pearce MS, Barge D, Braggins H, Cale CM, Goldblatt D, Gennery AR
Background
X-linked (XL) CGD, a rare primary immunodeficiency due to CYBB mutations leading to
defective gp91PHOX, results in decreased/absent respiratory oxidative burst. High rates of
discoid lupus have been reported in XL-carriers. Current literature about XL-CGD carrier
health is limited to small series and anecdotal reports. We undertook a large in-depth study
of XL-CGD carriers.
Methods
XL-CGD families were identified and XL-carriers recruited. Participants completed detailed
questionnaires about their medical health with particular attention to SLE and
gastrointestinal (GI) symptoms. Affected and unaffected groups were compared by t-tests to
see if age/neutrophil oxidative burst (NOB) were significant.
Results
71 recruited (study remains open). Mean age 43 years (3-77).
Mean NOB 50% (9-94%)
Photosensitivity, mouth ulcers and joint symptoms occurred in >60%.
GI symptoms present in >50%. 10 had undergone invasive investigations. 4 diagnosed with
Inflammatory Bowel Disease (IBD).
Recurrent Ulcers
Raynaud’s
Joint Pain
Photosensitivity
GI Symptoms
Recurrent Skin Abscess
Affected
54
25
45
52
37
6
Unaffected
17
46
26
19
34
65
Age was not significantly different in affected/unaffected groups.
NOB value was significant (p=0.02) only for recurrent skin abscess (lower value more
associated with abscesses).
Discussion
The study’s strength is the detail collected. It is the largest, most comprehensive study of XLCGD carriers to date.
The main finding is significant medical problems are more common and diverse than
previously considered. The overlap with IBD has not been previously described, highlighting
the association between CGD colitis and IBD.
XL-CGD carriers are at greater risk of medical problems than previously thought. Symptoms
do not correlate well with NOB or age. Greater awareness of potential medical problems is
required.
The Psychological Health of X-linked Carriers of Chronic Granulomatous Disease in the
United Kingdom
Battersby AC, McKendrick F, Pearce MS, Braggins H, Cale CM, Goldblatt D, Gennery AR
Background
CGD is a rare primary immunodeficiency consisting of recurrent infection and inflammation.
70% of UK cases are X-linked (XL). Female carriers are usually confirmed after a relative’s
diagnosis. XL carriers have several risk factors for psychological health problems; a family
member with chronic illness, their own medical problems and an association with SLE. SLE is
associated with anxiety and depression.
Methods
XL CGD carriers, identified as relatives of an index case from the CGD Registry, were
recruited. Participants completed validated psychological health questionnaires; Hospital
Anxiety and Depression Score (HADS) and Pediatric Inventory for Parents (PIP).
Data were compared to published norms and published data from comparable groups. A
HADS score above 7 (anxiety/depression) is abnormal[1]. Symptom frequency was
compared with parents of CF children [2]. HAD mean scores were compared with SLE
patients published data [3].
PIP scores distress due to parenting a chronically unwell child with sub-scores about
frequency (PIP-F) and severity (PIP-S). PIP’s validation in oncology patients provides
comparison data [4].
Results
HADS
54 completed
No significant difference between CGD carrier mothers and other relatives.
66% XL-CGD carriers greater than borderline anxiety, significantly more frequent than CF
parents.
Anxiety
Depression
CGD Carriers
9.6
5.0
SLE (High-Pain)
9
8
SLE (Low-Pain)
4
3
PIP
45 Mothers completed.
CGD scores similar to oncology parents, but higher PIP-F scores (p 0.006).
No correlation between PIP and anxiety/depression symptoms (r<0.3)
Discussion
CGD carriers had significant rates of anxiety, greater than that seen in CF parents. Lack of
correlation between HADS and PIP suggests the cause for anxiety was not solely related to
their child’s disease.
This study highlights that XL CGD carriers suffer unrecognised but potentially significant
psychological health problems which may impact upon their own lives and their ability to
cope with the medical needs of their affected children.
1.
2.
3.
4.
Zigmond, A.S. and R.P. Snaith, The Hospital Anxiety and Depression Scale. Acta
Psychiatrica Scandinavica, 1983. 67(6): p. 361-370.
Besier, T., et al., Anxiety, Depression, and Life Satisfaction in Parents Caring for
Children With Cystic Fibrosis. Pediatric Pulmonology, 2011. 46(7): p. 672-682.
Waldheim, E., et al., Health-related quality of life, fatigue and mood in patients with
SLE and high levels of pain compared to controls and patients with low levels of pain.
Lupus, 2013. 22(11): p. 1118-1127.
Streisand, R., Braniceki, S, Tercyak, KP, Kazak, AE, Childhood Illness-Related Parenting
Stress: The Pediatric Inventory for Parents. Journal of Pediatric Psychology, 2001.
26(3): p. 155-162.
QUALITY OF LIFE (QOL) IS REDUCED IN X-LINKED CARRIERS OF CHRONIC
GRANULOMATOUS DISEASE (CGD)
Background
X-linked (XL) CGD is a rare primary immunodeficiency due to mutations
in CYBB leading to defective gp91PHOX (an NADPH oxidase complex subunit)
resulting in decreased or absent respiratory oxidative burst.XL-carriers have a high
incidence of discoid lupus.Other symptoms are anecdotally reported.Carrier status is
usually confirmed after a relative has been diagnosed with CGD.
Methods
XL-CGD families were identified and carriers recruited.Participants completed a
validated QoL questionnaire; the SF36v2.Means for each domain were compared
with published UK norms using a one-sample t-test.
Results
49/78 XL-carriers (34 mothers) completed the SF36v2.
QoL was reduced in all domains.
Domain
CGD Carriers UK Norms (female age 35-54)[1] P-value
Physical Function 79.28 (29.4)
89.4(18.3)
0.0099
Role Physical
74.35(32.2)
84.0(32.0)
0.00235
Bodily Pain
66.24(30.5)
79.4(22.0)
0.002
General Health
56.31(28.5)
74.1(20.3)
0.00
Vitality
44.98(25.5)
58.2(19.9)
0.002
Social Function
69.68(29.5)
86.7 (20.5)
0.001
Role Emotional
71.88(31.3)
80.3 (33.6)
0.0341
Mental Health
63.16(16.8)
71.6(17.8)
0.005
Table 1:SF36 Mean Scores for CGD XL-Carriers and UK Norms
Discussion
This study demonstrates that QoL is reduced in XL-CGD carriers compared to
population norms.
There may be several reasons for this.We have demonstrated elsewhere that XLCGD carriers have more medical problems than previously described.The majority of
participants in this study (70%) were mothers of CGD children:the stresses
associated with caring for a child with CGD may adversely affect QoL.
The importance of this study is that XL-CGD carriers have not previously been
shown to have significant problems yet these findings demonstrate that QoL is
significantly reduced when compared with similarly aged women.
High Fatigue Levels in XL-CGD Carriers associated with raised serum IL-8
A Battersby, A Martin, J Tarn, F Ng, C Cale, D Goldblatt, A Gennery
Background
Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency, of which 70% of
cases are X-linked (XL). We have recently found that XL-CGD suffer from inflammatory
complications of CGD (ESID Poster).
Methods
During a study of health of XL-CGD carriers we investigated symptoms of excessive fatigue
using the Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF). Serum levels
of pro-inflammatory cytokines (IL-1α, IL-5, IL-8, IL-10, IL-17, TGFβ1, IFNα and IFN-γ) were
measured on stored serum from 52/81 subjects, collected during the original research
study, by Cytometric Bead Array (CBA) immunoassay using a BD Biosciences LSRFortessa™
cell analyser. Results were compared with inflammatory disease control groups of 10 high
and 10 low fatigue Sjogren’s disease patients and 15 healthy controls. XL-CGD carriers were
divided into two groups; those who reported fatigue and those that did not.
Results
50% of XL-CGD carriers reported suffering excessive fatigue, associated with significantly
higher scores in the MFSI-SF (p<0.01) XL-CGD carriers have significantly higher serum IL-8
levels than normal controls (p=), but similar levels to patients with Sjögrens disease.
XL-CGD carriers reporting high levels of fatigue have significantly higher IL-8 levels, than
those not reporting fatigue (p=0.017). No other cytokines reached statistically significant
different levels, between groups.
Discussion
XL-CGD carriers report higher fatigue levels than expected, and there is association between
fatigue and raised IL8 in carriers, and in patients with Sjorgren disease, suggesting a
biological explanation for the symptoms. IL1β levels were not significantly raised. Previous
studies have associated pro-inflammatory states with excessive fatigue. Further research is
required to evaluate this finding in XL-CGD carriers.